Trichomonas vaginalis is a sexually transmitted protozoan. Trichomoniasis account for 3 million symptomatic cases of vaginitis annually in U.S. women and is associated with nongonococcal urethritis, prostatitis and other urological conditions in men. The clinical spectrum of trichomoniasis ranges from florid disease to totally asymptomatic carriage. The major thrust of this proposal is a fundamental investigation of the pathogenic mechanisms of T. vaginalis. We will enlarge our collection of recent isolates which will be characterized according to clinical presentation and virulence-associated properties including: production of abscesses in mice, destruction of tissue culture cell monolayers and hemolytic activity. Variation in these properties will be investigated by clone selection of particular isolates. Experimental modification of virulence-associated characteristics of trichomonads will be accomplished by continuous passage in standard media, tissue culture and animals. Trichomonads kill target cells by direct contact, not by phagocytosis or extracellular cytotoxins. We will assay binding of radiolabeled T. vaginalis to tissue culture cell monolayers of human urogenital tract origin to define critical aspects of the initial adhesion event. Attention will be directed to the role of nonspecific factors as well as lectin-like molecules and parasite cytoskeletal function. We will then compare the adhesion process in isolates with clearcut differences in intrinsic virulence. Our long term goal is to identify critical factors which may be exploited for treatment of local disease or conversion of symptomatic disease into asymptomatic carriage. Antigenic analysis of T. vaginalis isolates may define particular changes associated with modification of virulence. We used a panel of monoclonal antibodies to demonstrate significant antigenic variation among T. vaginalis from different geographic areas. These antibodies will be used as immunologic probes to correlate immunologic and biologic properties of T. vaginalis, particularly paired isolates selected for differences in virulence. These studies are prerequisite for eventual development of a workable system for serogrouping T. vaginalis strains and improvement of current methods for diagnosis of trichomoniasis.